Phosphonamido thiazoles and their utility as insecticides

ABSTRACT

Compounds of the formula   IN WHICH R is alkyl; R1 is alkyl, alkenyl, alkynyl, benzyl, cyanoalkyl or alkylthioalkylene; R3 is hydrogen or alkyl; R4 is hydrogen, alkyl or alkylthioalkylene and the use of these compounds as insecticides and acaricides.

Fancher States Patent [191 [54] PHOSPHONAMIDO THIAZOLES AND THEIR UTILITY AS INSECTICIDES [75] Inventor: Llewellyn W. Fancher, Orinda,

Calif.

[73] Assignee: Staufier Chemical Company, New

York,N.Y.

[22] Filed: Oct. 29, 1971 [21] Appl. No.: 198,012

UNITED STATES PATENTS 3,591,600 7/1971 Fancher ..260/306.8 R

l I 1 I 3,723,450

1 1 Mar. 27, 1973 Primary Examiner-Alex Mazel Assistant ExaminerR. J. Gallagher Att0rneyDaniel C. Block et al.

57 ABSTRACT Compounds of the formula in which R is alkyl; R is alkyl, alkenyl, alkynyl, benzyl, cyanoalkyl or alkylthioalkylene; R is hydrogen or alkyl; R, is hydrogen, alkyl or alkylthioalkylene and the use of these compounds as insecticides and acaricides.

35 Claims, No Drawings PHOSPIIONAMIDO THIAZOLES AND THEIR UTILITY AS INSECTICIDES N RS l ar-L in which R is alkyl having one to four carbon atoms, inclusive; R is alkyl having one to eight carbon atoms, inclusive, alkenyl having three to six carbon atoms, inclusive, preferably three carbon atoms, alkynyl having three to six carbon atoms, inclusive,.preferably three carbon atoms, benzyl, cyano alkyl in which the alkyl group has one to four carbon atoms, inclusive, preferably one carbon atom, alkylthioalkylene having a total of two to six carbon atoms, preferably two carbon atoms; R;, is hydrogen or alkyl having one to four carbon atoms, inclusive, preferably methyl; and R is hydrogen, alkyl having one to four carbon atoms, inclusive, preferably methyl, or alkylthioalkylene having a total of from two to six carbon atoms, inclusive.

The compounds having the formula N--na It s 1 WY" 8 ms 11 in which R, R R R and R are as defined above can be prepared by the following reactions:

X represents a halogen such as chlorine, bromine or iodine.

The compounds of the instant invention can be prepared by the reactions depicted in the above equations. Selection of time, temperature and solvents can be made within wide limitations. Once the equations and reactants are known, the specific procedures can be varied and modified to accommodate and facilitate the reaction. The intermediate from equation (a), i.e., the phosphonamide salt, can be isolated or reacted in the same or different solvent, or the reaction can be carried through to completion without isolation.

To facilitate reaction (a), a non-reactive acid acceptor is used as a catalyst. In the following specific examples, triethylamine is used as the base, however, other non-reactive acid acceptors would be acceptable. Similarly, in reaction (b), it was found that the reaction can be promoted by a slightly basic medium. This can be accomplished by adding triethylamine as required.

The compounds of the present invention and their preparation are more particularly illustrated by the following examples. Following the examples is a table of compounds which are prepared according to the procedures described herein.

EXAMPLE I Preparation of 2(S-methyl ethyl phosphonamidodithioyl)-thiazole. Seven and fourtenths grams (7.4 g., 0.03 mole) of ethylthionophosphine sulfide was slurried in ml. of dry dioxane and to this mixture was added 7.0 grams (0.07 mole) of 2- aminothiazole at 25 C. The temperature was allowed to increase to 30. A white solid precipitated. The mixture was stirred and warmed at 4548 for 0.5 hours, cooled to 15 and 6.1 g. (0.06 mole) (8.4 ml.) of triethylamine was added followed by 9.9 g. (0.07 mole) (4.4 ml.) of methyl iodide. The mixture was stirred and warmed at 4248 for 1.5 hours. The dioxane was removed on a rotary evaporator and the residue dissolved in benzene and washed twice with dilute sodium chloride solution. The benzene solution, containing the product, was dried over anhydrous magnesium sulfate, filtered and the solvent removed on a rotary evaporator. There was obtained 15.1 g. of the title compound, a viscous liquid, n 1.6570.

EXAMPLE 11 Preparation of the Intermediate 2-(S-triethylammonium-ethyl phosphonamidodithioyl)-thiazo1e. Forty grams (40 g., 0.4 mole) of 2-aminothiazo1e was slurried in 200 ml. of benzene. To this slurry was added 81 g. (0.8 mole) (111 ml.) of triethylamine, followed by 52.1 g. (0.21 mole) of ethylthionophosphine sulfide with stirring. The temperature rose from 24 to 60 C. Stirring at ambient temperature was continued for 4 hours. The crystalline solid was filtered off and washed with diethyl ether and n-hexane. The product was filtered to remove the bulk of the solvent. The triethylamine salt still contained some solvent and weighed 140.1 g., m.p. 98-104 C. This intermediate was used directly in the next step. Preparation of Z-(S-n-butyl, ethyl pohsphonamidodithioyl)-thiazole. Thirteen grams (13 g., 0.04 mole) of the triethylamine salt, supra, was mixed with 30 m1. of dimethyl formamide and 7.4 g.

(0.04 mole) of n-butyl iodide was added. The mixture was tested and found to be slightly basic. The mixture was stirred at 5560 C. for 3 hours, then poured into water and extracted with benzene. The benzene phase the class lnsecta, comprising six-legged usually winged form s, as beetles, bugs, bees, flies, and so forth, but also to other allied classes of arthropods whose members are Wingless and usually have more than six legs, as

was washed with water, dried over anhydrous magnesi- 5 spiders, mites, ticks, centipedes, and wood lice.

um sulfate, filtered, and evaporated on a rotary The following insect species were used in evaluation evaporator. There was obtained 10.0 g. (81.3 percent tests for insecticidal activity:

of theory) of the title compound, n,, 1.5932. 1. Housefly (HF) Musca domestica (Linn.)

The following is a table of certain selected com- 2.Lygus Bug (LB) Lygus hesperus (Knight) pounds that are preparable according to the procedure 10 3. Beam Aphid (BA) Aphisfabae (Scop.) described herein. Compound numbers are assigned to The housefly (HF) was used in evaluation tests of each compound and are used throughout the selected compounds as insecticides by the following remainder ofthe application. procedure. A stock solution containing 100 ng/ml. of

TABLE 1 N R; R s

\1. l /PI\IJ S R1 R18 H Compound \I.P., C. Number R1 R3 R4 or 719 OH; H H 1.6570 01115 H H 1.6262 CH1 H H 92-95 C1H5 H H 1.6367 11-03117 H H 1.6199 1-C3H1 1 H H 1. 6052 CHz=CHCHz H H 1 6496 CH CCH: H H 1.6414 CH;1(CH2)7 II H 1 5564 11 c1115 cHmCHcmoH, 11 11 .5436 12 C1111 (011;)1011011, 11 11 1.5013

c111 o111)1.C11

0111((111111 11 11 1. 51132 (cgHmcnon 11411111 11 11 1.6037 1100111 11 11 1.6390 omscn, 11 11 1.0510 CH1 011.1 11 1.6544 cmc11=c111 c11 11 1.0303 011105011 GHQ 11 1.6446 CH3 czHsSCHz H 1, 6395 011.1 cHiscHz H 1.6608 CnHs CHaSCH: H 1. 6327 Other examples of compounds falling within the the toxicant in an appropriate solvent was prepared. generic formula presented herein, which are prepara- Aliquots of this solution were combined with 1 milble by the aforedescribed procedures and which may liliter of an acetone-peanut oil solution in a glass Petri be formulated into insecticidal and acaricidal composidi h d ll d t d Th li were there to and PP as harem Illustrated are: achieve desired toxicant concentration ranging from 100 ug/per Petri dish to that at which 50 percent mor- E g g g4 tality was attained. The Petri dishes were placed in a circular cardboard cage, closed on the bottom with cel- 51:1 gga gtcn 2:1 5:: lophane and covered on top with cloth netting. Twentyfive female houseflies, three to five days old, were introduced into the cage and the per cent mortality was recorded after 48 hours. The L -50 l r lNSECTlClDAL EVALUATION TESTS D 3 e ex pressed in terms of pg. per 25 female flies. The results The term insect is used herein in its broad comof this insecticidal evaluation test are given in Table ll mon usage to include spiders, mites, ticks and like pests which are not in the strict biological sense classified as insects. The term "insect" is used to refer not only to those small invertebrate animals belonging mostly to under HF."

In the lygus bug (LB) Lygus hesperus test, 10 to 25, 2-week old nymphs of lygus bug were placed in separate circular cardboard cages sealed on one end with cellophane and covered by a cloth netting on the other. Aliquots of the toxicants, dissolved in an appropriate solvent, were diluted in water containing 0.002 percent of a wetting agent, Sponto 221 (polyoxyether of alkylated phenols blended with organic sulfonates). Test concentrations ranged from 0.05 percent downward to that at which 50 percent mortality was obtained. Each of the aqueous suspensions of the candidate compounds were sprayed onto the insect through the cloth netting by means of a hand-spray gun. Percent mortality in each case recorded after 24 and 72 hours counts were made to determine living and dead insects. The LD-SO values expressed as per cent of toxicant in the aqueous spray were calculated and recorded. These values are reported under the column LB in Table II.

The insect species black bean aphid (BA) Aphis fabae (Scop.) .was also employed in the test for insecticidal activity. Young nasturtium (Tropaeolum sp.) plants, approximately 2 to 3 inches tall, were used as the host plants for the bean aphid. The host plant was infested with approximately 50-75 of the aphids. The test chemical was dissolved in acetone, added to water which contained a small amount of Sponto 221, an emulsifying agent. The solution was applied as a spray to the infested plants. Concentrations ranged from 0.05

percent downward until an LD-50 value was achieved. These results are given in Table 11 under the column BA.

ACARICIDAL EVALUATION TEST The two-spotted mite (25M), Tetranychus urticae (Koch), was employed in tests for miticides. Young pinto bean plants or lima bean plants (Phaseolus sp.) in the primary leaf stage were used as the host plants. The young pinto bean plants were infested with about 100 mites of various ages. Dispersions of candidate materials were prepared by dissolving 0.1 gram in ml. of a suitable solvent, usually acetone. Aliquots of the toxicant solutions were suspended in water containing 0.002% v/v Sponto 221, polyoxyethylene ether sorbitan monolaurate, an emulsifying agent, the amount of water being sufficient to give concentrations of active ingredient ranging from 0.05 percent to that at which 50 percent mortality was obtained. The test suspensions were then sprayed on the infested plants to the point of run off. After 7 days, mortalities of the postembryonic form was determined. The percentage of kill was determined by comparison with control plants which had not been sprayed with candidate compounds. The LD-SO value was calculated using wellknown procedures. These values are reported under the columns 2SM-PE and ZSM-Eggs, in Table II.

SYSTEMIC EVALUATION TEST This test evaluates the root absorption and upward translocation of the candidate systemic compound. The bean aphid (BA) Aphis fabae (Scop.) and two-spotted mite (28M) Tetranychus urticae (Koch), were employed in the test for systemic activity.

Young nasturtium (Tropaeolum sp.) plants were used as the host plants for the bean aphid. The host plants, 2-3 inches tall, were transplanted into 1 pound of soil that had been treated with the candidate compound. Immediately after planting in the treated soil, the plants were infested with 50-75 aphids of various ages. Concentrations of toxicant in the soil ranged from 10 ppm per pound of soil downward until an LD-SO value was obtained. Mortality was recorded after 72 hours.

The percentage of kill of the test species was determined by comparison with control plants placed in distilled water or untreated soil. The LD-50 values were calculated. These systemic test results are reported in Table 11 under the column BA-Sys.

Aliquots of the toxicant dissolved in an appropriate solvent are diluted in water and placed in glass bottles. Pinto bean plants (Phaseolus sp.) with expanded primary leaves were placed in the solutions so that the roots and major portion of the stem were completely immersed. Immediately after placement of the plants, the leaves were infested with 75-100 mites of various ages. Total mortality of adults, nymphs and eggs were recorded after one week. The LD-50 values expressed in ppm of toxicant in the aqueous suspensions are reported in Table II under the column ZSM-Sys."

TABLE II (LD-50 VALUES) 2SM Per Cent compound hf lb ba ba-sys. 2sm-sys. number ug/25+ p.p.m. pe eggs p.p.m. 1 1.7 .03 .003 0.8 .005 .03 .8 2 15 .05 .003 l .03 .05 10 3 3 .003 .0008 .3 .003 .008 1 4 16 .03 .003 3 .008 .03 3 S 30 .03 .03 3 .03 .03 8 6 .05 .03 10 .03 .03 5 7 10 .05 .003 1 .01 .03 l 8 4 .05 .003 10 .005 .03 .8 9 100 .05 .05 .05 1O 100 .05 10 .05 05 11 100 .05 .03 .05 .05 12 100 .05 .03 .05 .05

l3 100 .05 .05 .05 14 75 .05 .03 .05 .05 l5 100 .05 .05 .05 l6 100 .003 .05 .05 17 90 .05 .03 .05 .05 18 45 .05 .05 .05 .05 19 30 .003 05 05 20 25 .05 .008 8 .03 .05 3 21 45 .05 .03 .10 .05 .05 8 22 30 .01 .03 .005 .03 .8 23 100 .05 .03 .05 24 100 .05 .03 3 .03 .03 3 25 100 .05 .05 .05 .05

( indicates not tested for the indicated insect species) As those in the art are well aware, various techniques are available for incorporating the active component or toxicant in suitable pesticidal compositions. Thus, the

pesticidal compositions can be conveniently prepared in the form of liquids or solids, the latter preferably as homogeneous free-flowing dusts commonly formulated by admixing the active component with finely divided solids or carriers as exemplified by talc, natural clays, diatomaceous earth, various flours such as walnut shell, wheat, soya bean, cottonseed and so forth.

Liquid compositions are also useful and normally comprise a dispersion of the toxicant in a liquid media although it may be convenient to dissolve the toxicant directly in a solvent such as kerosene, fuel oil, xylene, alkylated naphthalenes or the like and use such organic solutions directly. However, the more common procedures is to employ dispersions of the toxicant in an aqueous medium and such compositions may be produced by forming a concentrated solution of the toxicant in a suitable organic solvent followed by dispersion in water, usually with the aid of surface active agents. The latter, which may anionic, cationic or nonionic types, are exemplified by sodium stearate,

potassium oleate and other alkaline metal soaps and detergents such as sodium lauryl sulfate, sodium naphthalene sulfonate, sodium alkyl naphthalene sulfonate, methyl cellulose, fatty alcohol ethers, polyglycol fatty acid esters, and other polyoxyethylene surface active agents. The proportion of these agents commonly comprise 1-15 percent by weight of the pesticidal compositions although the proportion is not critical and may be varied to suit any particular situation.

What is claimed is:

1. A compound of the formula in which R is alkyl having one to four carbon atoms, inclusive; R, is alkyl having one to eight carbon atoms, inclusive, alkenyl having three to six carbon atoms, inclusive, alkynyl having three to six carbon atoms, inclusive, benzyl, cyano alkyl in which the alkyl group has one to four carbon atoms, inclusive, alkylthioalkylene having a total of two to six carbon atoms; R is hydrogen or alkyl having one to four carbon atoms, inclusive; and R is hydrogen, alkyl having one to four carbon atoms, inclusive, or alkylthioalkylene having a total of from two to six carbon atoms, inclusive.

2. A compound according to claim 1 in which R is alkyl, R, is alkyl, R, is hydrogen and R, is hydrogen.

3. The compound according to claim 2 in which R is ethyl and R, is methyl.

4. The compound according to claim 2 in which R is ethyl and R, is ethyl.

5. The compound according to claim 2 in which R is methyl and R, is methyl.

6. he compound according to claim 2 m WhlCh R IS methyl and R, is ethyl.

7. The compound according to claim 2 in which R is ethyl and R, is n-propyl.

8. The compound according to claim 2 in which R is ethyl and R, is isopropyl.

9. The compound according to claim 2 in which R is ethyl and R, is n-octyl.

10. The compound according to claim 2 in which R is ethyl and R, is 3-methylbutyl.

11. The compound according to claim 2 in which R is ethyl and R, is isobutyl.

12. The compound according to claim 2 in which R is ethyl and R, is l-methylheptyl.

13. The compound according to claim 2 in which R is ethyl and R, is n-hexyl.

14. The compound according to claim 2 in which R is ethyl and R, is 2-ethylbutyl.

15. The compound according to claim 2 in which R is ethyl and R, is n-butyl.

16. A compound according to claim 1 in which R is alkyl, R, is benzyl, R is hydrogen and R is hydrogen.

17. The compound according to claim 16 in which R is ethyl.

18. A compound according to claim 1 in which R is alkyl, R, is alkenyl, R is hydrogen and R, is hydrogen.

19. The compound according to claim 18 in which R is ethyl, R, is Z-propenyl.

20. A compound according to claim 1 in which R is alkyl, R, is alkynyl; R is hydrogen and R, is hydrogen.

21. The compound according to claim 20 in which R is ethyl and R, is 2-propynyl.

22. A compound according to claim 1 in which R is alkyl, R, is cyano alkyl, R, is hydrogen and R, is hydrogen.

23. The compound according to claim 22 in which R is ethyl, R, is cyanomethyl.

24. A compound according to claim 1 in which R is alkyl, R, is alkylthioalkylene, R is hydrogen and R, is hydrogen.

25. The compound according to claim 24 in which R is ethyl and R, is methylthiomethylene.

26. A compound according to claim 1 in which R is alkyl, R, is alkyl, R,, is alkyl and R, is hydrogen.

27. The compound according to claim 26 in which R is ethyl, R, is methyl and R, is methyl.

28. A compound according to claim 1 in which R is alkyl, R, is alkenyl, R is alkyl and R, is hydrogen.

29. The compound according to claim 28 in which R is ethyl, R, is Z-propenyl and R is methyl.

30. A compound according to claim 1 in which R is alkyl, R, is alkynyl, R is alkyl and R, is hydrogen.

31. The compound according to claim 30 in which R is ethyl, R, is 2-propynyl and R is methyl.

32. A compound according to claim 1 in which R is alkyl, R, is alkyl, R, is alkylthioalkylene and R, is hydrogen.

33. The compound according to claim 32 in which R is ethyl, R, is methyl and R, is ethylthiomethylene.

34. The compound according to claim 32 in which R is ethyl, R, is methyl and R is methylthiomethylene.

35. The compound according to claim 32 in which R is ethyl, R, is ethyl and R, is methylthiomethylene. 

2. A compound according to claim 1 in which R is alkyl, R1 is alkyl, R3 is hydrogen and R4 is hydrogen.
 3. The compound according to claim 2 in which R is ethyl and R1 is methyl.
 4. The compound according to claim 2 in which R is ethyl and R1 is ethyl.
 5. The compound according to claim 2 in which R is methyl and R1 is methyl.
 6. The compound according to claim 2 in which R is methyl and R1 is ethyl.
 7. The compound according to claim 2 in which R is ethyl and R1 is n-propyl.
 8. The compound according to claim 2 in which R is ethyl and R1 is isopropyl.
 9. The compound according to claim 2 in which R is ethyl and R1 is n-octyl.
 10. The compound according to claim 2 in which R is ethyl and R1 is 3-methylbutyl.
 11. The compound according to claim 2 in which R is ethyl and R1 is isobutyl.
 12. The compound according to claim 2 in which R is ethyl and R1 is 1-methylheptyl.
 13. The compound according to claim 2 in which R is ethyl and R1 is n-hexyl.
 14. The compound according to claim 2 in which R is ethyl and R1 is 2-ethylbutyl.
 15. The compound according to claim 2 in which R is ethyl and R1 is n-butyl.
 16. A compound according to claim 1 in which R is alkyl, R1 is benzyl, R3 is hydrogen and R4 is hydrogen.
 17. The compound according to claim 16 in which R is ethyl.
 18. A compound according to claim 1 in which R is alkyl, R1 is alkenyl, R3 is hydrogen and R4 is hydrogen.
 19. The compound according to claim 18 in which R is ethyl, R1 is 2-propenyl.
 20. A compound according to claim 1 in which R is alkyl, R1 is alkynyl; R3 is hydrogen and R4 is hydrogen.
 21. The compound according to claim 20 in which R is ethyl and R1 is 2-propynyl.
 22. A compound according to claim 1 in which R is alkyl, R1 is cyano alkyl, R3 is hydrogen and R4 is hydrogen.
 23. The compound according to claim 22 in which R is ethyl, R1 is cyanomethyl.
 24. A compound according to claim 1 in which R is alkyl, R1 is alkylthioalkylene, R3 is hydrogen and R4 is hydrogen.
 25. The compound according to claim 24 in which R is ethyl and R1 is methylthiomethylene.
 26. A compound according to claim 1 in which R is alkyl, R1 is alkyl, R3 is alkyl and R4 is hydrogen.
 27. The compound according to claim 26 in which R is ethyl, R1 is methyl and R3 is methyl.
 28. A compound according to claim 1 in which R is alkyl, R1 is alkenyl, R3 is alkyl and R4 is hydrogen.
 29. The compound according to claim 28 in which R is ethyl, R1 is 2-propenyl and R3 is methyl.
 30. A compound according to claim 1 in which R is alkyl, R1 is alkynyl, R3 is alkyl and R4 is hydrogen.
 31. The compound according to claim 30 in which R is ethyl, R1 is 2-propynyl and R3 is methyl.
 32. A compound according to claim 1 in which R is alkyl, R1 is alkyl, R3 is alkylthioalkylene and R4 is hydrogen.
 33. The compound according to claim 32 in which R is ethyl, R1 is methyl and R3 is ethylthiomethylene.
 34. The compound according to claim 32 in which R is ethyl, R1 is methyl and R3 is methylthiomethylene.
 35. The compound according to claim 32 in which R is ethyl, R1 is ethyl and R3 is methylthiomethylene. 